Dynamics of NKT-Cell Responses to Chlamydial Infection

Abstract

Natural killer T (NKT) cells have gained great attention owing to their critical functional roles in immunity to various pathogens. In this review, we provide an overview of the current knowledge on the role of NKT cells in host defense against and pathogenesis due to Chlamydia, which is an intracellular bacterial pathogen that poses a threat to the public health worldwide. Accumulating evidence has demonstrated that NKT cells, particularly invariant NKT (iNKT) cells, play a crucial role in host defense against chlamydial infections, especially in C. pneumoniae infection. iNKT cells can promote type-1 protective responses to C. pneumoniae by inducing enhanced production of IL-12 by dendritic cells (DCs), in particular CD8α+ DCs, which promote the differentiation of naive T cells into protective IFN-γ-producing Th1/Tc1 type CD4+/CD8+ T cells. This iNKT-cell-mediated modulation of DC function is largely dependent upon CD40–CD40L interaction, IFN-γ production, and cell-to-cell contact. In addition, iNKT cells modulate the function of natural killer cells. NKT cells may be also involved in the pathogenesis of some chlamydial diseases by inducing different patterns of cytokine production. A better understanding of NKT-cell biology will enable us to rationally design prophylactic and therapeutic tools to combat infectious diseases.

Editorial: CD1- and MR1-Restricted T Cells in Antimicrobial Immunity

“…Perhaps even more intriguing, i NKT cell activation could have seemingly contradictory consequences during infection with different species of the same pathogen (e.g., Chlamydia spp.) ( 37 ). CD1d −/− and Jα18 −/− mice have been used extensively to address the contributions of i NKT cells in infection and immunity.…”

Insights into innate immune cell evasion by Chlamydia trachomatis

“…Activated type I NKT can promote the maturation and differentiation of DCs into CD8+/CD103+ DCs, which can further activate T cell differentiation into functional Th1 or Tc1-like peptide antigen-specific T cells. Activated antigen-specific CD4 + Th1 and CD8 + Tc1 can suppress bacterial infection ( 93 , 94 ). However, CD1d-restricted NKT cells can regulate the immune response to chlamydial infection and cause immunopathological damage.…”

Cross Talk Between Natural Killer T and Dendritic Cells and Its Impact on T Cell Responses in Infections

“…It was reported that these bacteria abundantly express glycosphingolipids (GSLs) which have high similarity in structures to a-GalCer. Our group studied the role of NKT cells in host defense against Chlamydiae, an intracellular bacterial pathogen that poses a threat to public health worldwide (29,30). We found that chlamydial glycolipid exoantigen (GLXA), a glycolipid antigen derived from Chlamydia muridarum, can activate iNKT cells at in vitro and in vivo settings.…”